John A Dawson

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.

Common scientific and statistical errors in obesity research.

This review identifies 10 common errors and problems in the statistical analysis, design, interpretation, and reporting of obesity research and discuss how they can be avoided. The 10 topics are: 1) misinterpretation of statistical significance, 2) inappropriate testing against baseline values, 3) excessive and undisclosed multiple testing and “P‐value hacking,” 4) mishandling of clustering in cluster randomized trials, 5) misconceptions about nonparametric tests, 6) mishandling of missing data, 7) miscalculation of effect sizes, 8) ignoring regression to the mean, 9) ignoring confirmation bias, and 10) insufficient statistical reporting. It is hoped that discussion of these errors can improve the quality of obesity research by helping researchers to implement proper statistical practice and to know when to seek the help of a statistician.

Changes in pediatric waist circumference percentiles despite reported pediatric weight stabilization in the United States.

Obesity is a global health concern but the United States has reported a leveling in obesity rates in the pediatric population.

Social status and energy intake: a randomized controlled experiment

While the inverse association between socioeconomic status (SES) and obesity in high gross domestic product countries is well established using observational data, the extent to which the association is due to a true causal effect of SES and, if so, the mechanisms of this effect remain incompletely known. To assess the influence of social status on obesity via energy intake, we randomized individuals to a higher or lower social status and observed subsequent energy intake.

The stated conclusions are contradicted by the data, based on inappropriate statistics, and should be corrected: comment on ‘intervention for childhood obesity based on parents only or parents and child compared with follow-up alone’: Difference in nominal significance level

Yackobovitch-Gavan et al. (1) executed a three-arm parallel randomized controlled trial (RCT). Participants were randomly assigned to one of three groups: a control group or one of two behavioural interventions, towards either both parents and children or parents only. The ‘primary outcome measures were the change in BMI-SDS [BMIstandard deviation score] from baseline at completion of the intervention (3 months) and at the end of follow-up (24 months) in each of the groups’. In parallel RCTs, the correct analyses for inferences about treatment effects compare outcomes among randomized groups (2–5). Yackobovitch-Gavan et al. did these analyses (‘comparison of the change in BMI-SDS after 3 months among the groups yielded no significant difference (P = 0.440)’) with similarly non-significant among-group findings at 24 months (P = 0.208). Therefore, the correct conclusion to draw for this study is that the data did not show that either of the treatment interventions was effective with respect to the primary outcomes. Instead, the abstract concludes that ‘[a]n intervention programme that focuses on both parents and children was found to have positive short-term and long-term effects on BMI-SDS’. The analytic strategy used to reach this conclusion, a DINS (difference in nominal significance) error, can result in an inflated Type-I error rate higher than 50% with more than two groups (3–5); its invalidity has been noted repeatedly in the literature (3–7). Because the primary conclusions communicated by Yackobovitch-Gavan and colleagues are not substantiated by the data, we believe that the paper should be corrected.

Immune system stimulation induced by Escherichia coli lipopolysaccharide alters plasma free amino acid flux and dietary nitrogen utilization in growing pigs

Changes in plasma free AA flux reflect the modification of AA metabolism in different metabolic states. Immune system stimulation (ISS) in growing pigs may redistribute AA from protein retention towards processes involved in the immune response, thus impacting AA utilization. The aim of the current study was to evaluate the effect of ISS on whole-body nitrogen (N) utilization and the kinetics of plasma free AA. Ten gilts (BW 9.4 ± 1.1 kg) were surgically fitted with jugular vein catheters, individually housed in metabolism crates, and feed-restricted (550 g/d). Repeated intramuscular injections of increasing amounts of Escherichia coli lipopolysaccharide (LPS) were used to induce ISS (30 and 36 µg/kg BW, given 48 h apart). Whole-body N-balance was determined for 3-d before ISS (ISS-) and 3-d during ISS (ISS+). At the end of each N-balance period, a bolus dose of labeled [U-13C, U-15N]-AA mixture (Ile, Leu, Lys, Met, Phe, Thr, Trp, Val, and Gln) was infused intravenously, followed by serial blood collection for determination of isotopic enrichment. A double exponential model was fitted with plasma enrichment data for each pig and each AA, and equation parameters were used to estimate plasma-free AA flux and pool size. Apparent ileal digestibility (AID) of N was determined using the slaughter technique and an indigestible marker. Blood samples were collected before and 76-h after the initiation of ISS and assayed for hematology and blood chemistry. Body temperature (BT) was monitored during the course of study. Blood chemistry, hematology, and BT results indicated that LPS induced effective ISS in pigs (P < 0.05). ISS tended to reduce N retention (P = 0.09) and the N retention-to-N intake ratio (P = 0.08). Apparent total tract digestibility of dietary energy and AID of N were reduced by ISS (P < 0.05). Plasma flux (µmol/kg BW/h) for Ile and Phe was reduced by ISS (P < 0.05). Strong tendencies for decreased Lys flux and N retention were observed in ISS pigs (P < 0.10). ISS increased the pool size for Leu but reduced the pool size for Ile (P < 0.05). Collectively, these results suggest that ISS alters the utilization of dietary N and AA flux, as well as pool size in growing pigs. The decrease in Lys, Phe, and Ile flux during ISS may be attributed to a reduction in whole-body protein synthesis or decreased catabolism of these AA. Relative to other AA, dietary Lys, Phe, and Ile requirements may decrease in ISS pigs.

Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity

Bariatric surgery induces significant weight loss, increases insulin sensitivity, and reduces mortality, but the underlying mechanisms are not clear. It was hypothesized that Roux‐en‐Y gastric bypass (RYGB) surgery improves metabolic profile along with weight loss. The objective of this pilot study was to evaluate changes in serum metabolites and fatty acids (FA) at 2 weeks and 6 months after RYGB.

Drawing conclusions from within-group comparisons and selected subsets of data leads to unsubstantiated conclusions: Letter regarding Malakellis et al.

Australian and New Zealand Journal of Public Health 2018 vol. 42 no. 2

Subjective social status is associated with compensation for large meals – A prospective pilot study

OBJECTIVESnSubjective social status (SSS) is known to be inversely associated with obesity. Our objective was to determine if SSS is associated with eating behaviors that would predispose to weight gain, specifically, with inadequate compensation for excess energy consumed during a single large meal. Therefore, we conducted a pilot study to determine the association of SSS with 24-h energy balance, 24-h and post-lunch energy intake, changes in body composition and changes in adjusted resting energy expenditure on days when a high-energy lunch was consumed in free-living human subjects.nnnMETHODnFemale participants (7 normal weight and 10 overweight) consumed 60% of estimated 24-h energy requirements as a lunchtime meal in the laboratory for 14 days. Subjective social status was measured at baseline using the MacArthur Scale. Remote Food Photography Method was used to record food intake outside of the lab on days 1-2, 7-8, and 12-13. Associations of 24-h energy balance, 24-h and post-lunch energy intake, changes in adjusted resting energy expenditure and changes in percent body fat (measured by dual x-ray absorptiometry) with SSS were studied.nnnRESULTSnMean (standard deviation) age and BMI were 36.29 (8.25) years and 26.43 (2.32) kg/m2, respectively. Lower SSS was significantly associated with positive energy balance (p for trend 0.002), and higher post-lunch energy intake (pu202f=u202f0.02) when controlled for age and initial body mass index.nnnCONCLUSIONSnOur pilot data show that lower SSS is associated with higher post-lunch energy intake, which is indicative of poor energy compensation following a large meal. Over a longer time period, this could result in fat mass gain. Studies that are of longer duration and well-powered are warranted to confirm our findings.

Examining Prefrontal Cortex Activity and Tonic Anxiety in Alcohol Use Disorder Recovery: A Functional Near Infrared Spectroscopy Study

ABSTRACT Cognitive impairment, emotional reactivity, and circuitry differences have been examined for anxiety using functional magnetic resonance imaging, positron emission tomography, and near infrared spectroscopy, with no overwhelming consensus as to the impacted brain regions. In the present study, 32 participants in recovery from alcohol use disorder were administered the Penn State Worry Questionnaire to assess tonic anxiety level and viewed aversive images during functional near infrared spectroscopy (fNIR) prefrontal cortex (PFC) assessment. Negative cue examination revealed a positive association between anxiety level and left dorsolateral and dorsomedial PFC activation. Previous alcoholism research demonstrates potential confounds in these dorsolateral and dorsomedial regions, limiting generalizations to addiction-naïve populations. However, fNIR presently showed reliability as an imaging technique for assessing anxiety-related PFC activity that could augment standard diagnostic procedures for anxiety disorders. In addition, this type of research could impact understanding of comorbidity in alcohol use disorder treatment and recovery.